Antidepressants can have numerous effects on sexual function including altered sexual desire, erection difficulties and orgasm problems. This systematic review investigated different ways to manage such sexual dysfunction. We included 23 randomised studies, with a total of 1886 participants who had developed their sexual problems while taking antidepressant medication. Twenty-two of these studies looked at the addition of further medication to the ongoing treatment for depression. For men with antidepressant-induced erectile dysfunction, the addition of sildenafil (Viagra; three studies, 255 participants) or tadalafil (Cialis; one study, 54 participants) appeared to improve the situation. For women with antidepressant-induced sexual dysfunction the addition of bupropion (Wellbutrin, Zyban; three studies, 482 participants) at higher doses appears to be the most promising approach studied so far, but further data from randomised trials are likely to be required before it can be recommended confidently. We did not find evidence that any intervention led to a worsening of psychiatric symptoms; however, we cannot be confident of this for many of the interventions studied, as only small numbers of participants have been studied so far.
The evidence currently available is rather limited. For men with antidepressant-induced erectile dysfunction, the addition of sildenafil or tadalafil appears to be an effective strategy. For women with antidepressant-induced sexual dysfunction the addition of bupropion at higher doses appears to be the most promising approach studied so far.
Sexual dysfunction (including altered sexual desire, orgasmic and ejaculatory dysfunction, erectile and other problems) is a relatively common side effect of antidepressant medication. These sexual side effects may compromise a person's lifestyle and result in a lack of compliance with the prescribed antidepressant to the detriment of the person's mental health. A wide range of management strategies are possible to address this problem, including behavioural, psychological and pharmacological approaches.
1. To determine the effectiveness of management strategies for sexual dysfunction caused by antidepressants.
2. To determine the adverse effects and acceptability of the different management strategies.
We searched the Cochrane Depression, Anxiety and Neurosis Group's Specialized Register (CCDANCTR, to 1 January 2013), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). Additional searches were carried out by the author team on the same biomedical databases (using terms for 'sexual dysfunction' only) together with CINAHL (1982 to Jan 2012). The reference lists of reports of all included studies were screened.
We included randomised controlled trials that compared management strategies for antidepressant-induced sexual dysfunction versus placebo or any alternative strategy.
Two authors independently extracted data and assessed trial quality. Study authors were contacted for additional information.
We included 23 trials involving 1886 people in this updated review. Twenty-two of these trials investigated the addition of medication to treat the identified dysfunction, with most agents studied in only single studies. One study investigated switching to an alternative antidepressant.
In men, data for the phosphodiesterase inhibitors sildenafil (three studies, 255 participants) and tadalafil (one study, 54 participants) indicated they led to a greater improvement in erectile function than placebo. Combined data from three sildenafil studies found benefit over placebo on International Index of Erectile Function ratings of ability to achieve (MD 1.04, 95% CI 0.65 to 1.44), and maintain erections (MD 1.18, 95% CI 0.78 to 1.59). A single point improvement on these ratings is equivalent to an improvement in frequency from 'sometimes' to 'most times'. Men receiving tadalafil were more likely to report improved erectile function (RR 11.50, 95% CI 3.03 to 43.67). For women it remains uncertain whether sildenafil is more effective than placebo. Unpublished data could reduce this uncertainty.
Data from three studies in men and women of bupropion 150 mg twice daily indicate a benefit over placebo on rating scale scores (SMD 1.60, 95% CI 1.40 to 1.81), but response rates in two studies of bupropion 150 mg once daily demonstrated no statistically significant difference in effect (RR 0.62, 95% CI 0.09 to 4.41).
Other augmentation strategies failed to demonstrate significant improvements in sexual dysfunction compared with placebo.
One trial involving 75 people with sexual dysfunction due to sertraline assessed the effect of changing antidepressant. Switching to nefazodone was significantly less likely to result in the re-emergence of sexual dysfunction than restarting sertraline (RR 0.34, 95% CI 0.19 to 0.60), however, nefazodone is no longer available for clinical use.
There is an absence of randomised trials assessing the effects of switching to currently-available antidepressant agents with lower rates of adverse sexual effects, the role of psychological or mechanical interventions, or of techniques such as drug holidays.
We identified no data for any of the strategies included in the trials assessed that indicated that they led to a worsening of psychiatric symptoms. However, the relatively small numbers assessed for many of the interventions studied means that the possibility of such an effect cannot confidently be excluded in all cases.
Given the small numbers of studies assessing most of the strategies assessed, the presence of any unpublished trials could have substantial effects on estimates of effect. In some cases, only results from particular items or subscales within ratings scales are available. It is likely that this could act to bias estimates of effect obtained, increasing apparent effectiveness.